Treatment of Comorbid Obesity and Major Depressive Disorder: A Prospective Pilot Study for their Combined Treatment

Background. Obese individuals who suffer from major depressive disorder are routinely screened out of weight loss trials. Treatments targeting obesity and depression concurrently have not been tested. Purpose. To test the short-term efficacy of a treatment that combined behavioral weight management and cognitive behavioral therapy (CBT) for obese adults with depression. Methods. Twelve obese females diagnosed with major depressive disorder received weekly group behavioral weight management, combined with CBT for depression, for 16 weeks. Weight, symptoms of depression, and cardiovascular disease (CVD) risk factors were measured at baseline and week 16. Results. Participants lost 11.4% of initial weight and achieved significant improvements in symptoms of depression and CVD risk factors. Conclusions. Obese individuals suffering from major depressive disorder can lose weight and achieve improvements in symptoms of depression and CVD risk factors with 16 weeks of combined treatment. A larger randomized controlled trial is needed to establish the efficacy of this treatment

Ghrelin and neuropeptide Y: Actions and interactions within the neuroanatomically distributed system for the control of feeding behavior

Ghrelin, a recently discovered peptide-hormone, has been portrayed as a hunger signal. It is produced in the gut and acts centrally to cause increases in food intake in humans and animals. It is widely believed that ghrelin\u27s orexigenic effect is mediated by the central Neuropeptide (NPY) system, although there are many locations within the brain at which the ghrelin-NPY interactions may take place. Most attention has been focused on the hypothalamus, to the neglect of potentially important contributions of the caudal brainstem (CBS), within which GHS-R (ghrelin\u27s receptor), and NPY neurons and receptors (R) are strongly represented. The studies presented in this dissertation broadly address the interactions between ghrelin and the NPY system, segregating pathways and integrative processes seated in different levels of the neuraxis. In addition to a forebrain site of action for the hyperphagic response to ghrelin, we identify a sensitive site within the CBS; we observed hyperphagic responses to ghrelin administration to both the 4th (hindbrain) ventricle and, with doses that were sub-threshold for the ventricle, to the brainstem parenchyma. We showed that activity of NPY Y1 R and Y5 R subtypes are both essential for responses to forebrain and CBS ghrelin delivery. In both cases the Y1 R contribution stems from receptor sub-populations within the CBS. Interestingly, the Y5 R contribution depended on injection site, with forebrain Y5 R activity required for the forebrain-elicited response, and a hindbrain receptor complement required for the 4th ventricle response. In separate studies we explored the site and Y R subtype selectivity requirements for the hyperphagic response to NPY itself. As for ghrelin, Y R subtype requirements varied with site of drug delivery. The profile obtained, however, was different from that described for ghrelin with respect to (1) the location of the relevant Y R subpopulations, and (2) the different combinatory principles by which Y1- and Y5 R-related signals are integrated (summation and OR gate for NPY; AND gate for ghrelin). We can firmly reject the hypothalamocentric perspective. Taken together, our results capture some of the richness of the neuroanatomically distributed system for the control of feeding behavior

Hyperphagic effects of brainstem ghrelin administration

The role of ghrelin in feeding control has been ad-dressed from a largely hypothalamic perspective, with little attention directed at ingestive consequences of stimulation of the peptide’s receptor, the growth hor-mone secretagogue receptor (GHS-R), in the caudal brainstem. Here, we demonstrate a hyperphagic re-sponse to stimulation of GHS-R in the caudal brainstem. Ghrelin (150 pmol) delivered to the third and fourth ventricles significantly and comparably increased cumu-lative food intake, with maximal response 3 h after injection. The meal patterning effects underlying this hyperphagia were also similar for the two placements (i.e., significant reduction in the time between injection and first-meal onset, an increase in the number of meals taken shortly after the injection, and a trend toward a